rs6066029

Variant names:

• chr20-46588889-C-T
• rs6066029
• NM_022829.6:c.1016+271G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022829.6(SLC13A3):​c.1016+271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,160 control chromosomes in the GnomAD database, including 1,460 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1460 hom., cov: 32)
• Consequence: SLC13A3 NM_022829.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 2 publications found

Genes affected

SLC13A3 (HGNC:14430): (solute carrier family 13 member 3) Mammalian sodium-dicarboxylate cotransporters transport succinate and other Krebs cycle intermediates. They fall into 2 categories based on their substrate affinity: low affinity and high affinity. Both the low- and high-affinity transporters play an important role in the handling of citrate by the kidneys. The protein encoded by this gene represents the high-affinity form. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been characterized yet. [provided by RefSeq, Jul 2008]

SLC13A3 Gene-Disease associations (from GenCC):

• leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022829.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	NM_022829.6	MANE Select	c.1016+271G>A		intron	N/A	NP_073740.2
	SLC13A3	NM_001011554.3		c.875+271G>A		intron	N/A	NP_001011554.1	Q8WWT9-6
	SLC13A3	NM_001193339.2		c.866+271G>A		intron	N/A	NP_001180268.1	Q8WWT9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A3	ENST00000279027.9	TSL:1 MANE Select	c.1016+271G>A		intron	N/A	ENSP00000279027.4	Q8WWT9-1
	SLC13A3	ENST00000495082.5	TSL:1	c.875+271G>A		intron	N/A	ENSP00000419621.1	Q8WWT9-6
	SLC13A3	ENST00000290317.9	TSL:5	c.875+271G>A		intron	N/A	ENSP00000290317.5	Q8WWT9-6

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19231 AN: 152042 Hom.: 1453 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.0738

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19257 AN: 152160 Hom.: 1460 Cov.: 32 AF XY: 0.130 AC XY: 9692 AN XY: 74394

African (AFR) AF: 0.0869 AC: 3606 AN: 41518

American (AMR) AF: 0.187 AC: 2865 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1850 AN: 5162

South Asian (SAS) AF: 0.0835 AC: 403 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10594

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8154 AN: 68000

Other (OTH) AF: 0.122 AC: 257 AN: 2108

Alfa AF: 0.117 Hom.: 178

Bravo AF: 0.131

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.66
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6066029; hg19: chr20-45217528;